A practical preparation of the key intermediate for penems and carbapenems synthesis

J Antibiot (Tokyo). 2013 Mar;66(3):161-3. doi: 10.1038/ja.2013.8.

Abstract

A novel, practical and stereoselective synthesis of (3R,4R)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidinone, a key intermediate in the preparation of β-lactam antibiotics is reported. The crucial step of the synthesis is based on the Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade between silyl protected (R)-3-butyn-2-ol and the nitrone derived from benzyl hydroxylamine and benzyl glyoxylate. The obtained adduct is subjected to debenzylation with sodium, or lithium in liquid ammonia followed by oxidation with lead tetraacetate to afford the final product.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonia / chemistry
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Carbapenems / chemical synthesis*
  • Carbapenems / chemistry
  • Lactams / chemical synthesis*
  • Lactams / chemistry
  • Lithium / chemistry
  • Organometallic Compounds / chemistry
  • Oxidation-Reduction
  • Sodium / chemistry
  • Stereoisomerism
  • beta-Lactams / chemical synthesis*
  • beta-Lactams / chemistry

Substances

  • 4-acetoxy-3-(1'-((tert-butyldimethylsilyl)oxy)ethyl)-2-azetidinone
  • Anti-Bacterial Agents
  • Carbapenems
  • Lactams
  • Organometallic Compounds
  • beta-Lactams
  • Ammonia
  • Lithium
  • Sodium
  • lead tetraacetate